PB2590: BREAKTHROUGH INVASIVE FUNGAL INFECTION CAUSED BY SCEDOSPORIUM APIOSPERMUM IN PEDIATRIC PATIENT WITH ACUTE MYELOID LEUKEMIA: DIAGNOSTIC, CLINICAL COURSE AND TREATMENT
Authors: María Pérez Raya, Eva María Calavia Aranda, Antonia Pascual Martínez, Nazaret Serrano García, Manuel Isidro Muñoz Pérez
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Scedosporium apiospermum opportunistic saprofhytic filamentous fungus. Its main mechanism of transmission is inhalation, apiratio of contaminated water or direct inoculation into tissues. Invasive fungal infection (IFI) appears in severely inmunocompromised patients, especially in acute myeloblastic leukemia (AML), prolonged neutropenia and allogeneic hematopoietic stem cell transplant (HSCT) recipients, with a high mortality rate. It mainly affects the lungs, skin or central nervous system and has angioinvasive capacity. Voriconazole iv remains the standard of care. Combination therapy with liposomal amphotericin B, isavuconazole, posaconazole, terbinafine or echinocandins seems to show superior results in patient with AML, allogeneic transplant recipients although it has not been adequately compared. In addition, debridement, immune reconstitution or reduction of immunosuppression are essential in its control. Aims: We report a case of pediatric patient who depelops breakthrough IFI caused by non-Aspergillus fungus in the context of AML induction. Methods: We present the case of a 10 years old male, native of Morocco, diagnosed with pre-T Acute Lymphoblastic Leukemia (ALL). He started treatment according to EORTC protocol and later FLA-Ida, being refractory. A haploidentical allo-HPTL was performed in sequential regimen, achieving complete remission (CR) with positive minimal residual disease (MRD). After infusion of donor lymphocytes he achieved negative MRD. On day +303 the patient presented a 1st relapse with a switch to myeloid phenotype. He started rescue therapy with Ida-FLA+Venetoclax as a bridge to 2nd allogeneic HSCT. Results: In aplasia after 2nd cycle of FLA+Venetoclax, the patient developed gum pain, with gingivitis and spontaneous exodontia of the canine. Fever was associated, without other focus of infection. Prophylaxis with acyclovir, trimethoprim-sulfamethoxazole, levofloxacin and liposomal amphotericin B was performed. In this context, he started empirical piperacillin/tazobactam with torpid evolution, appearance of necrotic eschar, bone exposure, daily fever and increase of acute phase reactants. Teicoplanin is associated, escalating to Meropenem and increasing liposomal amphotericin B to 5mg/kg. Serial cultures and dental exudates were negative. Cranial CT scan was compatible with collection in the gum. Necrotic tissue curettage was performed and samples were taken for pathology and microbiology, where Scedosporium apiospermum was isolated, with necrotic foci and angioinvasion, voriconazole iv was started and liposomal amphotericin B was maintained, withdrawing antibiotherapy. After initiation of antifungal bitherapy and surgical debridement, favorable evolution, completing treatment with amphotericin 43 days and voriconazole 58 days. Subsequently, 2nd prophylaxis with voriconazole is continued. The underlying disease was reevaluated and remained in CR. 2nd allogeneic HSCT of identical DNE was performed, reaching 2nd CR and negative EMR at 3 months. Summary/Conclusion: • Fungal infections by non-Aspergillus fungi can affect severely immunocompromised patients, such as allogeneic HSCT recipients or after prolonged neutropenia, with increasing incidence and high mortality despite the current therapeutic spectrum. • Diagnostic sampling, extension study and initiation of empirical antifungal therapy should be performed upon suspicion. • Voriconazole has demonstrated activity against S. apiospermum. Bitherapy with amphotericin has shown favorable results. Surgical debridement and immune reconstitution or reduction of immunosuppression are also essential.Keywords: Fungal infection, Hematopoietic cell transplantation, Infant, Acute leukemia